Organ-on-Chip Technology for Aerobic Intestinal Host – Anaerobic Microbiota Research

The Aerobic intestinal Host – Anaerobic Microbiota (AHAM) interface is an important tissue barrier in our intestine where the microbiota resides in close proximity and in symbiosis with ourselves: the host. A disturbance in this delicate balance between our cells and the commensal microorganisms is associated with effects on the host's health and/or the microbiota. These host-microbiota interactions are believed to be influenced by several factors, which hampers the study of the effect of a single element exclusively. Organ-on-chips (OoCs), microengineered in vitro cell culture models, aim to mimic the physiologically relevant microenvironment of organs. These OoCs can be used to mimic the AHAM interface and study the host-microbiota interactions in a well-controlled environment. In this review, we summarize existing models for (components of) the AHAM interface and provide an overview of four different AHAM-on-chip systems. Furthermore, we defined challenges that need to be taken in consideration when designing or using an AHAM-on-chip, such as the importance of oxygen modulation, sensors and choice of chip material. It is essential to achieve a balance between the accuracy of representing the in vivo interface and the (technical) attainability of the in vitro AHAM-on-chip. The technological and biological aspects make an AHAM-on-chip extremely complex, which emphasizes the need for a multi-disciplinary team. We believe that standardization and higher throughput systems are crucial to accelerate the development of OoC technology.